Preliminary results from the 4 mg maintenance period of the FREEDOM study, the first in which perampanel has been examined as monotherapy, were presented at the 2019 International Epilepsy Congress in Bangkok.
James Wheless, MD
Perampanel (Fycompa, Eisai) is safe, effective, and well-tolerated as monotherapy in previously untreated patients with partial-onset seizures (POS) or primary generalized tonic-clonic seizures, according to preliminary data presented at the 2019 International Epilepsy Congress, June 22-26, in Bangkok, Thailand.
The antiepileptic drug is a selective, non-competitive AMPA (alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid) receptor antagonist that was first approved by the FDA in 2012 for the adjunctive treatment of POS. It is currently being evaluated in a phase 3, multi-center, open-label, uncontrolled study (FREEDOM; NCT03201900) in patients age 12 and older with POS with or without secondary generalized seizures.
The ongoing study, which includes patients from Japan and South Korea, consists of a 6-week titration period followed by a 26-week, 4 mg per day maintenance period. If a patient experiences seizures during the maintenance period, they are titrated up to 8 mg per day perampanel, followed by a 26-week maintenance period.
The primary end point is seizure freedom during the 4 mg maintenance period.
Researchers led by Takamichi Yamamoto, MD, presented findings from 89 patients who had received perampanel. Of note, 44.9% and 43.8% of patients (mean age, 42.1) were categorized as symptomatic or cryptogenic, respectively. Among the cohort, complex partial seizures (60.7%) and complex partial with secondary generalized seizures (64%) were the most common, with a median baseline seizure frequency of 2 seizures per 3 months.
Notably, 16 patients discontinued use during the initial titration period, with 73 entering the 4 mg per day maintenance period, of whom 46 completed. Twenty-one of those patients entered the 8 mg per day maintenance period. The data presented was analyzed following the completion of the 26-week maintenance period.
Among those included in the 4 mg intent to treat population, 63% achieved seizure freedom (46/73; 95% CI, 50.9-74.0), and 65% (n = 31/48) of those with secondarily generalized seizures were convulsive seizure free. Treatment-emergent adverse events were reported in 78.7% of patients (70/89; including treatment and extension phases), with the most common being dizziness (33.7%), somnolence (13.5%), nasopharyngitis (13.5%), and headache (11.2%), all of which are consistent with the drug’s known safety profile.
“When selecting an antiepileptic drug for my patients, I consider benefits of single pill dosing which can reduce overall pill burden, hopefully making it easier for patients to adhere to their treatment schedule as early as possible while taking into account tolerability,” said James Wheless, MD, chair, Division of Pediatric Neurology, Le Bonheur Children's Hospital in Memphis, Tennessee, in a statement.
Perampanel is also FDA-approved as adjunctive therapy for primary generalized tonic-clonic seizures in patients with epilepsy age 12 and older, as well as monotherapy for POS with or without secondary generalized seizures in patients with epilepsy age 12 and older.
The drug, which is available in tablet form and oral suspension, is unique in that it has a long half-life, with pharmacokinetic data demonstrating no significant impact of a missed dose on plasma levels.
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Yamamoto T, Kim J-H, Lim S-C, et al. Efficacy and safety of perampanel monotherapy in previously untreated patients with partial-onset seizures (POS): primary analysis of Study 342 (FREEDOM study). Presented at: 2019 International Epilepsy Congress. June 22-26, 2019; Bangkok, Thailand. Poster 315.